V3 antagonists for the treatment or prevention of chronic pain

Abstract

The present invention relates to a V 3 antagonist for use in the treatment of chronic pain, in particular neuropathic pain.

1 - 3 . (canceled) 
   
   
       4 . A method of treatment of chronic pain comprising administering a pharmaceutically effective amount of a V 3  antagonist to a subject in need thereof. 
   
   
       5 . The method of treatment according to  claim 4 , wherein the V 3  antagonist is selected from:
 (2S,4R)-1-[5-chloro-1-(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide;   2-[2-(3-Chloro-4-fluorophenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide;   N-Isopropyl-2-[2-(3-methoxyphenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]acetamide;   2-[2-(4-Fluoro-3-methoxyphenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide;   2-[2-(3-Chlorophenyl)-6-[3-(4-hydroxypiperidin-1-yl)propoxy]-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide;   2-[2-(3-Chlorophenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide;   (S)-(+)-2-[2-(3-Chlorophenyl)-6-(2-methyl-3-pyrrolidin-1-ylpropoxy)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide;   2-[6-(5-Dimethylaminomethyl-2-fluorophenyl)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide;   2-[6-(3-Dimethylaminomethylphenyl)-2-(4, fluoro-3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide;   N-tert-Butyl-2-[2-(3-chlorophenyl)-4-oxo-6-(3-pyrrolidin-1-ylpropoxy)-4H-quinazolin-3-yl]acetamide and   2-[6-(3-Dimethylaminomethylphenyl)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide   or a pharmaceutically acceptable salt or solvate thereof.   
   
   
       6 . The method of treatment according to  claim 4 , wherein the chronic pain is neuropathic pain. 
   
   
       7 . The method of treatment according to  claim 4 , wherein the chronic pain is inflammatory pain. 
   
   
       8 . The method of treatment according to  claim 4 , wherein the subject is a mammal. 
   
   
       9 . The method of treatment according to  claim 8 , wherein the mammal is human. 
   
   
       10 . A pharmaceutical composition comprising a V 3  antagonist selected from (2S,4R)-1-[5-chloro-1-(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide;
 2-[2-(3-Chloro-4-fluorophenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide;   N-Isopropyl-2-[2-(3-methoxyphenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]acetamide;   2-[2-(4-Fluoro-3-methoxyphenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide;   2-[2-(3-Chlorophenyl)-6-[3-(4-hydroxypiperidin-1-yl)propoxy]-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide;   2-[2-(3-Chlorophenyl)-4-oxo-6-(3-piperidin-1-ylpropoxy)-4H-quinazolin-3-yl]-N-isopropylacetamide;   (S)-(+)-2-[2-(3-Chlorophenyl)-6-(2-methyl-3-pyrrolidin-1-ylpropoxy)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide;   2-[6-(5-Dimethylaminomethyl-2-fluorophenyl)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide;   2-[6-(3-Dimethylaminomethylphenyl)-2-(4, fluoro-3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide;   N-tert-Butyl-2-[2-(3-chlorophenyl)-4-oxo-6-(3-pyrrolidin-1-ylpropoxy)-4H-quinazolin-3-yl]acetamide and   2-[6-(3-Dimethylaminomethylphenyl)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide   or a pharmaceutically acceptable salt or solvate thereof.